Why animal studies cannot suitably assess nanomedicines

Engineered nanoparticles are being increasingly investigated as a way to improve medicinal products by overcoming problems with bioavailability, stability and toxicity. Although nanotechnology has already been widely used by the industry, regulators are only just beginning to consider whether nanotechnology may pose significant risks to human health. They have also realised that existing testing paradigms using animal models may be insufficient.

Nanotechnology has infiltrated a number of consumer markets and represents a rapidly expanding multibillion dollar global market that is predicted by the US National Science foundation to be worth more than $1 trillion by 2015.1 In particular, nanotechnology has offered numerous benefits to the pharmaceutical and healthcare sectors, with many nanoenabled medical products now readily available (Table 1). Other nanotech innovations, including carbon nanotubebased RNA, DNA, protein and drug delivery systems are also in development.3 Indeed, between 2004 and 2005 there was a 60% increase in the number of nano-enabled productsin the development pipeline and around 1000 or so products on the global market.4

Unfortunately, it is not yet clear whether nanomaterials may pose risks to human safety. Medically relevant nanomaterials can be a mixture of particles with biologically important size, charge distribution and chemistry characteristics, which makes it difficult to predict what effects they may have. In June 2007, the European Scientific Committee on Emerging and Newly Identified Health Risks recommended that the potential risks of nanoparticles be considered in light of evidence that they can cross biological barriers impervious to larger entities and their bulk equivalents;5 for instance, it is known that 20–50 nm nanoparticles can cross the blood brain–barrier and that 70 nm particles can cross into the pulmonary system. In addition, spherical fullerenes appear to accumulate in the liver.6,7

In this article, we consider whether existing in vivo approaches are predictive of the effects of nanoenabled products on human patients. The prospects for replacing animal studies with alternative models are also discussed.

For the purpose of this article, the term nanoparticle is used to describe a chemical, compound material or complex that has a unit size in at least one-dimension that does not exceed 100 nm. Nanoenabled therapeutic delivery systems, diagnostic or monitoring tools are nanodevices based on the definition of a medical device as given by the Medical Devices Directive 93/42/EEC.8